Stress Inoculation-Induced Indications of Resilience in Monkeys
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Journal of Traumatic Stress, Vol. 20, No. 4, August 2007, pp. 423–433 (
C 2007)
Stress Inoculation-Induced Indications
of Resilience in Monkeys
David M. Lyons and Karen J. Parker
Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center,
Stanford, CA
The negative consequences of stress are well-recognized in mental health research. Exposure to early life
stressors, for example, increases the risk for the development of mood, anger, anxiety, and substance abuse
disorders. Interestingly, however, early life stressors have also been linked to the subsequent development
of resilience. Variously described as inoculating, immunizing, steeling, toughening, or thriving, the
hypothesis that early life stressors provide a challenge that, when overcome, induces adaptations that
enhance emotional processing, cognitive control, curiosity, and neuroendocrine regulation is examined
in this review of squirrel monkey research.
Early exposure to severe forms of stress is a risk factor Garmezy, 1991; Rutter, 1993; Yates, Egeland, & Sroufe,
for the development of subsequent psychopathology (Agid 2003). In this review, we summarize our studies designed
et al., 1999; Davidson, Stein, Shalev, & Yehuda, 2004; Foa, to test the hypothesis that early life stressors may foster the
Stein, & McFarlane, 2006; Heim, Plotsky, & Nemeroff, development of resilience as modeled in squirrel monkeys.
2004). Far less researched, but of equal importance, are Monkeys raised in groups comprised of 3–4 mother–
indications that early life stressors may also foster resilience. infant pairs were initially randomized to a stress inocula-
Adults cope better with spousal loss, illness, and major tion protocol or a no-stress control condition at 17 weeks of
accidents if they have previously experienced and coped age. The stress inoculation protocol consisted of 10 weekly
with stressors in childhood (Forest, 1991; Khoshaba & 1-hour social separations (Parker, Buckmaster, Schatzberg,
Maddi, 1999). Work-related stressors likewise have fewer & Lyons, 2004) designed to provide repeated opportunities
depressive effects in adults previously exposed to work- for emotional activation and cognitive processing while not
related stressors in adolescence (Mortimer & Staff, 2004). overwhelming the capacity for coping with adversity. Dur-
These findings suggest that stressful events that are not ing each 1-hour separation session, each monkey was indi-
overwhelming, but challenging enough to elicit emotional vidually placed in a cage with various toy-like objects, and
activation and cognitive processing may make subsequent could see, hear, and smell, but not touch other unfamiliar
coping efforts more efficient, and therefore easier and more monkeys. Separations evoked repetitive distress peep-calls,
likely to be used later in life (Fergus & Zimmerman, 2005; locomotor agitation, and acute elevations in plasma cortisol
Supported by the Nancy Pritzker Network for the Study of Depression, and Public Health Service grants DA16902, MH77884, MH66573, and MH47573. The authors declare no
competing interests. All procedures were approved by Stanford University’s Administrative Panel on Laboratory Animal Care and were carried out in accordance with the NIH Guide
for the Care and Use of Laboratory Animals.
Correspondence concerning this article should be addressed to: David M. Lyons, Psychiatry Neuroscience, Stanford University Medical Center, 1201 Welch Road, MSLS P104–Mail
Code 5485, Stanford, CA 94305-5485. E-mail: dmlyons@stanford.edu.
C 2007 International Society for Traumatic Stress Studies. Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/jts.20265
423424 Lyons and Parker
levels with baseline measures restored soon after each so-
cial reunion with the natal group (Coe, Glass, Wiener, &
Levine, 1983; Hennessy, 1986; Stanton & Levine, 1985).
Separations were scheduled at weekly intervals to allow
ample time for recovery at an age when squirrel monkeys
are typically developing physical and psychosocial inde-
pendence (Boinski & Fragaszy, 1989; Rosenblum, 1968).
The transition from filial, mother-directed behavior (e.g.,
clinging and nursing) to exploratory, other-directed be-
havior (e.g., object exploration and social play) presents
important learning opportunities that are thought to pro-
mote the development of psychosocial functions (Lyons,
1993; Mason, 1971).
EMOTIONAL AND PSYCHOSOCIAL
INDICATIONS OF RESILIENCE
At 9 months of age, each monkey was tested along with
its mother for 30 minutes on 5 consecutive days in a novel
environment that contained an assortment of foods and ob-
Figure 1. Emotional and psychosocial indications of re-
jects (Parker et al., 2004). Similar test conditions have been silience are enhanced by stress inoculation. Measures of (A)
used to demonstrate that prior exposure to overwhelming time spent clinging to mother and (B) frequency of object ex-
postnatal stressors increases indications of anxiety-related ploration during repeated novel environment test sessions are
presented for stress inoculated (n = 11) and noninoculated
psychopathology in marmoset monkeys and macaques
(n = 9) monkeys (M + SEM ). A significant postnatal stress
(Andrews & Rosenblum, 1993; Dettling, Feldon, & Pryce, inoculation treatment-by-test session interaction ( p < .05)
2002; Hinde & Spencer-Booth, 1971). Here the novel en- was discerned for both measures (adapted from data presented
vironment stress test was used to assess stress inoculation- in Parker et al., 2004).
induced indications of resilience.
The behavior of stress inoculated and noninoculated
monkeys was initially similar, but differences emerged over calls and more time spent near peers (Levine & Mody,
repeated test sessions in the novel environment (Figure 1). 2003; Lyons, Martel, Levine, Risch, & Schatzberg, 1999).
Gradually, stress-inoculated compared to noninoculated
monkeys appeared to become less anxious as inferred by Cognitive Indications of Resilience
decreased maternal clinging and increased object explo-
ration. As described elsewhere in greater detail (Parker At 1.5 years of age, the stress inoculated and noninoculated
et al., 2004), these results indicate that stress inoculated monkeys were administered a test to examine prefrontal-
monkeys more readily self-regulate arousal and engage in dependent cognitive control of behavior described else-
more exploration than noninoculated monkeys. This con- where in detail (Parker, Buckmaster, Justus, Schatzberg, &
clusion is consistent with earlier findings from different Lyons, 2005). Briefly, a clear Plexiglas box with one open
cohorts of stress-inoculated monkeys that responded to the side was baited with a favorite food treat. When the box
removal of mothers at weaning with fewer distress peep- opening was oriented straight toward the monkey, food
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.Stress Inoculation in Monkeys 425
retrieval was achieved by reaching straight into the box.
When the box was rotated 90 degrees so the opening was
oriented toward either side, inhibition of straight-reaching
and a detour-reach around either side was required to
retrieve food from the clear baited box. Reaches aimed
straight toward the center of the box when the opening
was oriented toward either side were scored as response
inhibition errors.
Inhibitory control of the reaching response in marmoset
monkeys and rhesus macaques is impaired by lesions of pre-
frontal cortex (Diamond, 1990; Dias, Robbins, & Roberts,
1996; Wallis, Dias, Robbins, & Roberts, 2001), but not Figure 2. Prefrontal-dependent cognitive response inhibi-
lesions of the hippocampus (Diamond, Zola-Morgan, & tion is enhanced by stress inoculation. Stress inoculated mon-
Squire, 1989). Response inhibition assessed on this test is keys (n = 11) completed more successful test trials with the
box opening oriented toward either side compared to non-
also impaired in a marmoset monkey model of parental ne- inoculated monkeys (n = 9) examined over successive test
glect (Pryce, Dettling, Spengler, Spaete, & Feldon, 2004), days (mean + SEM). Maximum score is 6 successful tri-
and in squirrel monkeys treated with cortisol according to als per day. A significant postnatal stress inoculation treat-
a protocol that simulates a chronic stress response (Lyons, ment main effect ( p < .05) was discerned over repeated test
days. From “Prospective Investigation of Stress Inoculation
Lopez, Yang, & Schatzberg, 2000). Here this test of cog- in Young Monkeys,” by K. J. Parker, C. L. Buckmaster,
nitive control was used to assess stress inoculation-induced A. F. Schatzberg, and D. M. Lyons, 2004, Archives of General
indications of resilience. As indicated below, prefrontal- Psychiatry, 61, 933–941. Copyright 2004 by the American
dependent cognitive control likely plays a role in emotion Medical Association. Adapted with permission.
regulation and resilience.
Initially, each monkey was administered 10 trials per
day for 7 consecutive days with the box opening always These results are in keeping with evidence that postna-
oriented straight toward the monkey subject. Food re- tal stress inoculation stimulates the development of larger
trieval was achieved by reaching straight into the center prefrontal cortical volumes without affecting hippocam-
of the box. These 70 trials served to reinforce as prepotent pal volumes determined in squirrel monkeys by high-
the straight-reaching response. Thereafter, each monkey resolution magnetic resonance imaging (MRI; Lyons, Afar-
was administered 10 trials per day for 14 consecutive days ian, Schatzberg, Sawyer-Glover, & Moseley, 2002; Lyons,
with the orientation of the box opening systematically var- Yang, Sawyer-Glover, Moseley, & Schatzberg, 2001). Pre-
ied to assess inhibitory control of the straight-reaching frontal corticolimbic circuits play a key role in cognitive
response. The stress inoculated and noninoculated mon- control of behavior in humans and monkeys (Garavan,
keys performed equally well on all trials except for those Ross, & Stein, 1999; Konishi, Nakajima, Uchida, Sekihara,
that required inhibitory control of the straight-reaching & Miyashita, 1998; Lyons et al., 2000; Miller & Cohen,
response. Performance on the side-facing trials improved 2001; Ridderinkhof, Ullsperger, Crone, & Nieuwenhuis,
gradually over repeated test days (Figure 2), but at peak 2004). Increased prefrontal activation, for example, cor-
levels of performance all stress-inoculated monkeys suc- responds with diminished amygdala activation, and with
cessfully completed all response inhibition trials whereas increased cognitive control of emotion in humans stud-
fewer than half of the noninoculated monkeys achieved ied by functional MRI (Ochsner & Gross, 2005; Taylor,
similar levels of success. Eisenberger, Saxbe, Lehman, & Lieberman, 2006; Urry
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.426 Lyons and Parker
et al., 2006). In ongoing research we plan to assess whether
stress inoculation enhances prefrontal inhibition of amyg-
dala activity in monkeys.
CURIOSITY AND EXPLORATION-BASED
INDICATIONS OF RESILIENCE
At 2.5 years of age, the stress-inoculated and noninocu-
lated monkeys were administered a test to examine cu-
riosity and the exploratory behavior it elicits. This was
accomplished by monitoring exploration of novel and fa-
miliar objects presented in a stress-free condition (Parker
et al., 2007). Briefly, a familiar and a novel object were
each secured to the back wall of a test compartment. The
compartment was affixed to the monkey’s home cage 5
minutes before the start of each test, after which time a
sliding door was removed and the monkey had free access
to the test compartment. Test sessions lasted 30 minutes
in duration, and each monkey was tested on 5 consecutive
days. Similar test situations have been used to demon-
strate that prior exposure to overwhelming postnatal stres-
sors reduces exploration of novelty in macaque monkeys
(Hinde & Spencer-Booth, 1971; Roder, Timmermans, &
Vossen, 1989; Sackett, 1972). Here exploration of novelty
was used to assess stress inoculation-induced indications
of resilience. As described below, information-seeking and Figure 3. Curiosity and exploratory behavior are enhanced
sensory types of curiosity play a role in the maintenance of by stress inoculation. Measures of (A) latency to enter the
life-long resilience. test compartment, (B) frequency of entries into the compart-
ment, and (C) duration of time spent inside the compartment
All stress inoculated and all but one of the noninoculated across repeated test sessions are presented for stress inoculated
monkeys approached the test compartment and looked (n = 11) and noninoculated (n = 9) monkeys (M + SEM ).
inside. However, more stress inoculated than noninocu- A significant postnatal stress inoculation treatment main ef-
lated monkeys entered the compartment, and stress inoc- fect ( p < .05) was discerned across repeated test sessions
for all three measures of behavior. From “Early Life Stress
ulated monkeys entered faster, with greater frequency, and and Novelty Seeking Behavior in Adolescent Monkeys,” by
spent more time inside the test compartment compared to K. J. Parker, K. L. Rainwater, C. L. Buckmaster, A. F.
noninoculated monkeys (Figure 3). In addition, more Schatzberg, S. E. Lindley and D. M. Lyons, 2007, Psychoneu-
stress-inoculated than noninoculated monkeys explored roendocrinology, in press. Copyright 2007 by Elsevier Ltd.
Adapted with permission.
the objects inside the compartment, and stress-inoculated
monkeys preferred to explore the novel compared to the cantly more object exploration compared to noninoculated
familiar object (Parker et al., 2007). monkeys (Figure 1). Object exploration in the earlier study
In the earlier novel environment stress test conducted at was assessed, however, in inescapable conditions that in-
9 months of age, inoculated monkeys also showed signifi- volved involuntary separation of monkeys from the home
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.Stress Inoculation in Monkeys 427
cage. Both stress inoculated and noninoculated monkeys
in the earlier study presented with significantly higher cor-
tisol levels immediately after the novel environment stress
test compared to baseline levels measured in undisturbed
home cage conditions (Parker et al., 2004). Moreover, be-
cause posttest levels of cortisol were significantly lower in
stress inoculated compared to noninoculated monkeys, dif-
ferences in objection exploration in the earlier study were
confounded with differences in stress-related anxiety.
In the study conducted at 2.5 years of age, exploratory
behavior was assessed in the test compartment attached to
each monkey’s home cage. To further reduce the poten-
tially stressful nature of the test situation, each monkey
was extensively acclimated to the procedures and test com- Figure 4. Conceptual model of how stress fosters the devel-
partment prior to the start of the study. Stress hormones opment of resilience.
measured immediately after Test Sessions 1 and 5 con-
firmed that posttest cortisol levels were not significantly
different from baseline levels in undisturbed home cage
conditions at 2.5 years of age. Moreover, neither base- pared to noninoculated monkeys. Information-seeking and
line nor posttest cortisol levels correlated with measures sensory types of curiosity motivate individuals to seek
of exploration in the stress-free conditions at 2.5 years of new opportunities for action (Reio, Petrosko, Wiswell, &
age. Individual differences previously observed in object Thongsukmag, 2006). Engagement in new situations that
exploration at 9 months of age were, however, correlated entail challenging, but not overwhelming stress may further
with the rank order of individual differences in test com- induce neuroadaptations that enhance cognitive control
partment entries, r s = .41, p < .05, and total time spent and emotional self-regulation. According to this concep-
in the test compartment, r s = .51, p < .05, at 2.5 years of tual working model (Figure 4), curiosity thereby plays a role
age. Individual differences previously observed in cognitive in the life-long maintenance of stress inoculation-induced
control of behavior at 1.5 years of age were also correlated resilience.
with test compartment entries, r s = .48, p < .05, and total
time spent in the test compartment, r s = .42, p < .05, at
2.5 years of age. IS STRESS INOCULATION-INDUCED
Taken together, these data suggest that postnatal stress RESILIENCE MATERNALLY MEDIATED?
inoculation affects interrelated aspects of cognitive con-
trol, emotion regulation, and curiosity consistently ex- Stress inoculation-induced resilience in monkeys resembles
pressed over time and across situations. Exploration of nov- the effects of postnatal handling in studies of rats. Neona-
elty reflects more than diminished anxiety because stress- tal rats removed from the nest and briefly separated from
inoculated monkeys are more curious than noninoculated nest-related cues respond with behavioral and physiological
monkeys when tested in the absence of adrenocortical or indications of arousal (Hofer, 1996; Lyons & Banks, 1982).
behavioral indications of anxiety. Exploration of novelty When studied as adults, these rats then display increased ex-
and curiosity does not, in turn, reflect impulsivity because ploration, diminished emotionality, improved learning and
stress-inoculated monkeys more readily exercise cognitive memory, and diminished activation of the hypothalamic–
control and successfully inhibit impulsive behavior com- pituitary–adrenal (HPA) axis by various stressors relative to
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.428 Lyons and Parker rats that are raised in undisturbed conditions (Fernandez- hypothesis thus predicts that offspring removed along with Teruel et al., 2002; Levine, 2000; Meaney et al., 1996). their mother will not develop resilience due to diminished In rats, these outcomes seem to reflect the effects of levels of maternal care. In contrast, the stress-inoculation maternal behavior directed toward pups that are briefly hypothesis predicts that resilience will develop in monkeys separated and returned to the nest (Denenberg, 1999; exposed to either intermittent separation condition because Smotherman & Bell, 1980). Brief intermittent separations both conditions elicit acute anxiety and transiently activate increase maternal licking and grooming not only immedi- the HPA axis. ately after reunion, but also throughout postnatal develop- Unlike brief separations in rats, neither separation con- ment (Lee & Williams, 1974). Importantly, the neuroen- dition in monkeys caused a permanent increase in lev- docrine indications of resilience observed in rats exposed to els of maternal behavior (Parker et al., 2006). Moreover, brief intermittent postnatal separations can be replicated in group differences in maternal behavior did not correspond unmanipulated offspring that naturally receive high levels with the development of neuroendocrine indications of of maternal care (Liu et al., 1997). That increased maternal resilience. Juvenile monkeys exposed with their mother to care is sufficient to produce resilience in rats is corroborated repeated separations received less maternal care in the home by evidence that the amount of maternal stimulation re- cage throughout development compared to juveniles sepa- ceived by pups during development is negatively correlated rated alone, or juveniles from undisturbed groups. Yet both with later stress-induced activation of the HPA axis (Liu separation conditions induced in juvenile monkeys subse- et al., 1997; Rosenberg, Denenberg, & Zarrow, 1970). quent neuroendocrine indications of resilience compared To determine whether the development of resilience in to juveniles not exposed to either separation condition. monkeys exposed to intermittent separations is maternally Specifically, juveniles separated alone or separated along mediated, we recently examined maternal behavior and with their mother exhibited diminished cortisol responses subsequent neuroendocrine measures of resilience in 30 to a subsequent novel environment stress test compared to monkeys randomized to three postnatal treatment condi- monkeys that were not previously exposed to either of the tions (Parker, Buckmaster, Sundlass, Schatzberg, & Lyons, two separation conditions (Parker et al., 2006). 2006). In one condition, each juvenile monkey was sepa- rated from its mother and the natal group for 10 weekly sessions that each lasted 1-hour in duration. In the sec- ond condition, each juvenile monkey and its mother were LONG-LASTING NEUROENDOCRINE EFFECTS removed together from the group for 10 weekly 1-hour ses- OF STRESS INOCULATION sions. Both of these two conditions elicit distress peep-calls, locomotor agitation, and transiently activate the HPA axis The findings described above suggest that the development with baseline measures restored soon after reunion with the of resilience corresponds more closely to prior stress expo- natal group (Coe et al., 1983; Jordan, Hennessy, Gonzalez, sure than to differences in the quantity or quality of mater- & Levine, 1985). In the third condition, nonseparated nal care. A follow-up experiment confirmed this conclusion monkeys remained in their natal groups. in a different cohort of squirrel monkeys exposed from 10– The maternal mediation hypothesis predicts that juve- 22 weeks of age to a high-demand foraging condition or a nile monkeys exposed alone to repeated separations will low-demand foraging control. During the 12-week high- receive consistently more maternal care than age-matched demand condition, squirrel monkey mothers stopped car- undisturbed monkeys. Conversely, the repeated removal of rying their juvenile offspring at earlier ages and spent more both mothers and offspring will diminish maternal behav- time foraging for food (Lyons, Kim, Schatzberg, & Levine, ior as stressed mothers direct their attention toward rein- 1998). Plasma cortisol levels were intermittently higher tegration with the natal group. The maternal mediation in high-demand compared to low-demand offspring, but Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.
Stress Inoculation in Monkeys 429
foraging demands did not affect postnatal growth, nursing of HPA axis activation because endogenous cortisol cannot
behavior, or amounts of solid-food consumed. be distinguished from exogenous hydrocortisone (Lyons
By selectively reducing certain aspects of maternal et al., 2004).
care, squirrel monkey mothers seem to protect their A significant postnatal foraging condition-by-
offspring from the full impact of the stressful forag- hydrocortisone pretreatment interaction was discerned
ing task (Lyons et al., 1998). A similar process appears in postrestraint measures of ACTH with baseline levels
to occur in studies of bonnet macaques. Whereas un- controlled as a statistical covariate. Subsequent analysis
predictable variable-demand foraging conditions impair of simple main effects confirmed that monkeys from
emotional (Rosenblum & Andrews, 1994) and neurobio- the high-demand condition responded with diminished
logical (Coplan et al., 2006) aspects of development, con- activation of the HPA axis determined by smaller increases
sistently predictable high-demand foraging does not ap- in postrestraint ACTH levels compared to monkeys
pear to adversely affect development in bonnet macaques from the low-demand condition after pretreatment with
(Rosenblum & Paully, 1984). saline (Figure 5). As expected, hydrocortisone suppressed
Based on these findings, we studied squirrel monkeys postrestraint stress levels of ACTH, but enduring postnatal
raised in consistently high- versus low-demand foraging effects were not discerned when restraint was preceded
conditions for subsequent differences in neuroendocrine by hydrocortisone to test for differences in sensitivity to
indications of resilience (Parker et al., 2006). The maternal glucocorticoid feedback.
mediation hypothesis predicts that diminished levels of ma- In rodents, neuroendocrine indications of resilience are
ternal care induced by high-demand foraging will increase induced by maternal stimulation and mediated, in part, by
subsequent HPA axis responses to stress in monkeys pre- enhanced sensitivity to glucocorticoid feedback (Liu et al.,
viously raised in the high- versus low-demand condition. 1997; Meaney et al., 1996). In monkeys, we failed to find
Conversely, if early life stressors foster the development of evidence for maternal mediation or enhanced sensitivity to
resilience, then HPA axis responses to subsequent stressors glucocorticoid feedback. Our finding that increased mater-
in adulthood should be diminished in the monkeys raised nal stimulation is not required to foster resilience does not,
in high- versus low-demand foraging conditions. however, diminish the role of parenting in primate devel-
In midlife adulthood at ∼8 years of age, restraint stress opment. In our studies (Lyons et al., 1998), mother–infant
tests were administered to squirrel monkeys raised from attachment relationships were established well before on-
10–22 weeks of age in high- versus low-demand conditions. set of the postnatal protocols and all monkeys received
Restraint is a well-studied psychological stressor in ani- more than the typical levels of maternal care experienced
mal biomedical research (Glavin, Pare, Sandbak, Bakke, & in naturalistic conditions (Boinski & Fragaszy, 1989). Psy-
Murison, 1994). An intramuscular injection of saline was chosocial support derived from attachment relationships
given 60 minutes before initiation of the first 30-minute promotes coping skills in humans (Cohen & Wills, 1985)
restraint stress. Seven days later, an intramuscular injec- and nonhuman primates (Harlow & Suomi, 1974; Mason
tion of exogenous cortisol (i.e., 2.5 mg/kg hydrocortisone & Capitanio, 1988), and a minimal threshold of mater-
sodium succinate) was given 60 minutes before the second nal care is likely required for the development of stress
and otherwise identical restraint stress test. This dose of inoculation-induced resilience.
hydrocortisone was used to assess glucocorticoid feedback,
and is known to suppress stress-induced increases in squir- SUMMARY AND CONCLUSIONS
rel monkey adrenocorticotropic hormone (ACTH; Lyons,
Yang, Eliez, Reiss, & Schatzberg, 2004). Plasma levels of The studies reviewed above suggest that repeated ex-
ACTH were determined 0, 30, and 60 minutes after com- posure to early life stressors that are challenging, but
pletion of each restraint stress test, and analyzed as an index not overwhelming foster the development of interrelated
Journal of Traumatic Stress DOI 10.1002/jts. Published on behalf of the International Society for Traumatic Stress Studies.430 Lyons and Parker
molecular explanations of stress resistance (Maier, Amat,
Baratta, Paul, & Watkins, 2006; Meaney & Szyf, 2005).
Differences in prefrontal neuroanatomy limit prospects for
rodent research (Ongur & Price, 2000; Preuss, 1995),
and access to human brain tissue occurs less often than
in other fields of medicine where tissue biopsies are per-
formed. In the rare case where human brain tissue is made
available for biomedical research, the absence of prior psy-
chosocial measures precludes direct comparisons between
molecular, cellular, psychological, and social indications of
resilience. In this regard, nonhuman primates offer attrac-
tive opportunities to provide cross-disciplinary explana-
tions for the development of stress-inoculation induced
resilience. A better understanding of stress inoculation
through repeated exposure to stressors is important because
of concerns that reexperiencing stressors may impede re-
covery instead of fostering the development of resilience
(Bisson, Jenkins, Alexander, & Bannister, 1997; Foa,
Zoellner, Feeny, Hembree, & Alvarez-Conrad, 2002;
Figure 5. Neuroendocrine indications of resilience are en- Hembree et al., 2003; Mayou, Ehlers, & Hobbs, 2000).
hanced by stress inoculation. Postrestraint stress levels of
ACTH at successive 30-minute intervals after pretreatment
with (A) saline or (C) hydrocortisone, and the corresponding
time-integrated levels (B and D), are presented for 6–7 adult
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